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What is known: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer’s disease (AD). Objective: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. Methods: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. Results: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F = 4·12, d.f. = 1, P = 0·04; CDR: F = 4·12, d.f. = 1, P = 0·04). There were no significant differences in the two groups in terms of observed adverse events. What is new and conclusion: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for. [ABSTRACT FROM AUTHOR]

What is known: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer’s disease (AD). Objective: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. Methods: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. Results: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F = 4·12, d.f. = 1, P = 0·04; CDR: F = 4·12, d.f. = 1, P = 0·04). There were no significant differences in the two groups in terms of observed adverse events. What is new and conclusion: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for. [ABSTRACT FROM AUTHOR]

Abstract: Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world''s most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30mg/day (BD) (Group 1) and capsule of fluoxetine 20mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F =0.13, d.f.=1, P =0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified. [Copyright &y& Elsevier]

Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0·05 and 0·2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse–Geisser correction; F = 7·30, d.f. = 1·68, P = 0·002; F = 8·21, d.f. = 1·19, P = 0·004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor ( F = 4·17, d.f. = 1, P = 0·048; F = 4·29, d.f. = 1, P = 0·045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms ( P = 0·23). The difference between the two groups in the frequency of side effects was not significant. The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial. [ABSTRACT FROM AUTHOR]

Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression. A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment. The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation. The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's disease.Design: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran.Methods: Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease assessment scale (ADAS-cog) and Results: At four months, Melissa officinalis extract produced a significantly better outcome on cognitive function than placebo (ADAS-cog: df = 1, F = 6.93, p = 0.01; CDR: df = 1, F = 16.87, p < 0.0001). There were no significant differences in the two groups in terms of observed side effects except agitation, which was more common in the placebo group (p = 0.03).Conclusions: Melissa officinalis extract is of value in the management of mild to moderate Alzheimer's disease and has a positive effect on agitation in such patients. [ABSTRACT FROM AUTHOR]

Summary Background: Alzheimer's disease is characterized by a slow, progressive decline in cognitive function and behaviour. Acetylcholine esterase inhibitors are the only agents approved by the Food and Drug Administration for the treatment of Alzheimer's disease. All other agents prescribed for the treatment of Alzheimer's disease are used on an off-label basis. Current research into new drugs is focused on agents that will prevent, slow down and/or halt the progress of the disease process. Savia officinalis has been used in herbal medicine for many centuries. It has been suggested, on the basis of traditional medicine, its in vitro cholinergic binding properties and modulation of mood and cognitive performance in humans, that Salvia officinalis might potentially provide a novel natural treatment for Alzheimer's disease. The objective of this study was to assess the efficacy and safety of Salvia officinalis extract using a fixed dose (60 drops/day), in patients with mild to moderate Alzheimer's disease, over a 4-month period. Methods: This was a 4-month, parallel group, placebo-controlled trial undertaken in three centres in Tehran, Iran. Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42, 18 women) with a score of ≥12 on the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-cog) and ≤2 on the Clinical Dementia Rating (CDR) were randomized to placebo or fixed dose of S. officinalis extract. Over the 16 weeks, the main efficacy measures were the change in the ADAS-cog and CDR-Sum of Boxes scores compared with baseline. In addition, side-effects were systematically recorded throughout the study using a checklist. Results: At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placebo (ADAS-cog: F = 4·77, d.f. = 1, P = 0·03) (CDR-SB: F = 10·84, d.f. = 1, P < 0·003). There were no significant differences in the two groups in terms... [ABSTRACT FROM AUTHOR]

OBJECTIVE: Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers/activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia. METHODS: Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study. RESULTS: Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores. CONCLUSION: The results of this study present a novel application for potassium channel openers/activators in the neuropsychiatric disorders and diazoxide may be an effective adjuvant agent in the management of schizophrenia. [ABSTRACT FROM AUTHOR]

Summary Objective: Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers/activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia. Methods: Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study. Results: Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores. Conclusion:... [ABSTRACT FROM AUTHOR]

Objective: Passionflower (Passiflora incarnata) is a folk remedy for anxiety. A double-blind randomized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder. Methods: The study was performed on 36 out-patients diagnosed with GAD using DSM IV criteria. Patients were allocated in a random fashion: 18 to the Passiflora extract 45 drops/day plus placebo tablet group, and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial. Results: Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder. No significant difference was observed between the two protocols at the end of trial. Oxazepam showed a rapid onset of action. On the other hand, significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam. Conclusion: The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage. A large-scale trial is justified. [ABSTRACT FROM AUTHOR]

Objective: Clonidine-based therapies have been utilized as the main protocol for opiate detoxification for several years. However, detoxification with clonidine has its limitations, including lack of efficacy for mental symptoms. Accumulating evidence shows the efficacy of Passiflora incarnata extract in the management of anxiety. In our continuing study of traditional medicines, which have neurotropic effects, this plant had an anxiolytic effect, which may be used as an adjuvant agent in the detoxification of opiates by clonidine. We present the results of a double-blind randomized controlled trial of clonidine plus passiflora extract vs. clonidine plus placebo in the outpatient detoxification of 65 opiates addicts. Methods: A total of 65 opiates addicts were assigned randomly to treatment with passiflora extract plus clonidine tablet or clonidine tablet plus placebo drop during a 14-day double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. The fixed daily dose was 60 drops of passiflora extract and a maximum daily dose of 0·8 mg of clonidine administered in three divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). Conclusion: Both protocols were equally effective in treating the physical symptoms of withdrawal syndromes. However, the passiflora plus clonidine group showed a significant superiority over clonidine alone in the management of mental symptoms. These results suggested that passiflora extract may be an effective adjuvant agent in the management of opiate withdrawal. However, a larger study to confirm our results is warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Baclofen is known for the alleviation of signs and symptoms of spasticity. Reports from our previous study have suggested that it may be at least as effective as clonidine in the management of physical symptoms of opiate withdrawal syndromes and superior to clonidine in the management of mental symptoms. We now report on a randomized double-blind comparison of baclofen vs. clonidine in view of side-effects profile. METHODS: A total of 62 opiates addicts were randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine. This trial medication was given three times per day in divided doses. The severity of side-effects was measured in days 0, 1, 2, 3, 4, 7 and 14. RESULTS: There was no significant difference between two treat7ments in terms of retention in treatment (dropout) and overall side-effect. Nevertheless, significantly more problems relating to hypotension were encountered with subjects on clonidine. CONCLUSION: We conclude that, the low incidence of hypotension with baclofen suggests that the drug may be suitable for outpatient ambulatory treatment of withdrawal from opiates. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of Baclofen for the alleviation of signs and symptoms of spasticity. Comparison in view of side-effects profile; Management of the mental symptoms of opiate withdrawal; Significance of baclofen over clonidine in outpatient management of opiate detoxification.

Background: A variety of detoxification methods have been utilized for the treatment of opiate withdrawal syndrome, of which alpha-adrenergic agonists have attracted considerable attention over the last two decades. However, accumulating evidence in rats shows the efficacy of the GABAB receptor agonist, baclofen, in reducing alcohol intake and self-administration of cocaine. Objective: To examine the ability of baclofen, in the management of opiate withdrawal. Method: A total of 62 opiate addicts randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0·8 mg for clonidine given three times a day in divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). Results: Baclofen and clonidine were equally effective in treating the physical symptoms of withdrawal syndromes. However, baclofen showed a significant superiority over clonidine in the management of mental symptoms. Conclusion: These results suggest that baclofen might be a novel therapeutic agent for opiate withdrawal syndrome. However, a larger study to confirm our results is warranted. [ABSTRACT FROM AUTHOR]

SUMMARY Objective: There is a growing interest in investigating the role of glutamate receptors in the pathophysiology of schizophrenia. Indeed, the hyperdopaminergic theory of schizophrenia can explain only the positive symptoms of schizophrenia, whereas the glutamate hypothesis may provide a more comprehensive view of the illness. We undertook a trial to investigate whether the combination of haloperidol with piracetam, a nootropic agent which modulates the glutamate receptor positively was more effective than haloperidol alone. Methods: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 14 to haloperidol 30 mg/day plus piracetam 3200 mg/day and 16 to haloperidol 30 mg/day plus placebo. Results: Although both protocols significantly de- creased the score of the positive symptoms, the negative symptoms, the general psychopathological symptoms and the total score of PANSS scale over the trial period, the combination of haloperidol and piracetam showed a significant superiority over haloperidol alone in the treatment of schizophrenic patients. Conclusion: Piracetam, a member of the nootropic class of drugs and a positive modulator of glutamate receptor, may be of therapeutic benefit in treating schizophrenic patients in combination with typical neuroleptics. However, a larger study to confirm our results is warranted. [ABSTRACT FROM AUTHOR]

SUMMARY Discoveries made over the past 20 years have greatly improved our understanding of how the brain functions. This article focuses on the relation between memory and cellular mechanisms of neuronal and synaptic plasticity in the hippocampus. Several studies indicate that the hippocampal formation is a crucial element of the neurobiological bases of higher cognitive function. Severe damage to the hippocampal formation is known to produce seemingly permanent anterograde amnesia. A generally accepted hypothesis in neurobiology has been that long-lasting activity-dependent changes in the efficacy of synaptic transmission in the mammalian brain are considered to be of fundamental importance for the development of neural circuitry and for the storage of information. The most compelling and reliable model for such changes has been long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. Therefore, the possibility of the discovery and development of compounds that, by modulating hippocampal synaptic plasticity, would be useful for the management of dementia and amnesia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: There is growing interest in investigating the role of 5-HT receptors in the physiopathology of schizophrenia in particular the negative symptoms. Indeed, newer atypical antipsychotics which interact with 5-HT receptors are more effective in the treatment of negative symptoms compared to typical neuroleptics. We undertook a trial to investigate whether the combination of haloperidol with cyproheptadine, a relatively safe serotonin-blocking agent was more effective than haloperidol alone. METHODS: Thirty patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were allocated in a random fashion, 15 each to haloperidol 30 mg/day plus cyproheptadine 24 mg/ day and haloperidol 30 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the positive and negative symptom score over the trial period, the combination of haloperidol and cyproheptadine showed significant superiority over haloperidol alone in the treatment of the negative symptoms. CONCLUSION: Cyproheptadine is a relatively safe compound and may be of therapeutic benefit in treating negative symptoms of schizophrenia in combination with typical neuroleptics. However, a larger study to confirm our results is warranted. [ABSTRACT FROM AUTHOR]

SummaryObjective: There is growing interest in investigating the role of 5-HT receptors in the physiopathology of schizophrenia in particular the negative symptoms. Indeed, newer atypical antipsychotics which interact with 5-HT receptors are more effective in the treatment of negative symptoms compared to typical neuroleptics. We undertook a trial to investigate whether the combination of haloperidol with cyproheptadine, a relatively safe serotonin-blocking agent was more effective than haloperidol alone. Methods: Thirty patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were allocated in a random fashion, 15 each to haloperidol 30 mg/day plus cyproheptadine 24 mg/day and haloperidol 30 mg/day plus placebo. Results: Although both protocols significantly decreased the positive and negative symptom score over the trial period, the combination of haloperidol and cyproheptadine showed significant superiority over haloperidol alone in the treatment of the negative symptoms. Conclusion: Cyproheptadine is a relatively safe compound and may be of therapeutic benefit in treating negative symptoms of schizophrenia in combination with typical neuroleptics. However, a larger study to comfirm our results is warranted. [ABSTRACT FROM AUTHOR]

Assesses the safety and efficacy of Salvia officinalis extract for patients with mild to moderate Alzheimer's Disease (AD) over a period of four months. Use of randomized, double blind, placebo controlled trials in three centers in Iran; Use of Fisher's exact to analyze demographic data and frequency of side effects; Author's conclusion that the basic daily living activities and cognitive function improved with Salvia officinalis (sage) extract.

Compares the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe depression. Use of Hamilton Rating Scale for measuring depression; Superior efficacy of nortriptyline over fluoxetine; Frequency of autonomic side effects from nortriptyline.

Investigates the efficacy of ethinylestradiol as an adjuvant agent in the treatment of premenopausal women with chronic schizophrenia in an eight week double blind and placebo trial. Measurement of schizophrenia using positive and negative syndrome scale (PANSS) score; Performance of Fisher's exact test for comparison of demographic data; Author's conclusion that oestrogen maybe an effective adjuvant agent in the management of premenopausal women with acute schizophrenia.

QUESTION: Is hydroxyzine safe and effective for generalized anxiety disorder in adult outpatients?DesignRandomised trial. Investigators and participants were blind to treatment allocation.Setting89 French general practices (supervised by psychiatrists); January 1998-March 1999.Participants334 outpatients diagnosed with generalised anxiety disorder (DSM-IV criteria) and a Hamilton Rating Scale for Anxiety (HAM-A) total score of at least 20. All were aged 18-65 years (mean 45 years); 68% women. Exclusion criteria were alcohol or drug dependence; major depressive episode within 6 months; score of 7 or above on the Raskin Severity of Depression and Mania scale; psychotic or delusional disorders within 3 years; chronic disease; prostate cancer; closed angle glaucoma; antidepressants, neuroleptics, mood regulators, morphine or derivatives, hydroxyzine, or bromazepam within 4 weeks; benzodiazepines more than 2 days per week during the past 30 days; benzodiazepines during the previous 2 weeks; need for psychotherapy; contraindication to study medication; and women who were pregnant, breastfeeding or not using contraception.InterventionAfter a 2 week placebo run in phase, participants received 12 weeks of 50 mg hydroxyzine per day, 6 mg bromazepam per day or placebo. Treatment was divided into three daily doses. Treatment was followed by 4 weeks of run out placebo. 83% of participants completed treatment. Adherence to medication was 85%.Main outcome measuresResponse (mean change in HAM-A total score); remission; adverse effects.Main resultsCompared with placebo, after 3 months of treatment the hydroxyzine group had superior response rates (P=0.003); remission rates (P=0.028); changes in Clinical Impressions Severity score (P=0.001); maintenance of efficacy (P=0.022), and Hospital Anxiety and Depression scale score on day 84 (P=0.008). There was no significant difference in efficacy between hydroxyzine and bromazepam. Safety was comparable between groups. Drowsiness was the most commonly reported adverse effect in the hydroxyzine group, although drowsiness was twice as common with bromazepam (see table).ConclusionsHydroxyzine appears to be safe and effective in adults with generalised anxiety disorder. [ABSTRACT FROM AUTHOR]

Introduction: The possible effect of inflammatory factors on decreasing BDNF has been proposed in the literature. There is conflicting evidence regarding association between BDNF level alteration and treatment response in depressive patients undergoing electroconvulsive therapy (ECT). This study investigated the effects of celecoxib in manic patients undergoing ECT on treatment response and BDNF levels. Methods: This randomized, double-blind, clinical trial included 35 manic patients who received either celecoxib (200 mg twice daily) or placebo, from one day before the 1st ECT session throughout the 6th session. BDNF levels were measured at baseline, 1st, 3rd and 6th ECT sessions. Young mania rating scale was used to assess treatment response. Results: Adding celecoxib was not associated with a significant rise in BDNF levels following ECT. No difference was noted between groups in terms of treatment response. No significant association was found between changes in BDNF levels and patients' responses. Discussion: Adjuvant celecoxib did not significantly affect the BDNF level or the treatment response following ECT in manic patients. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3–6% of school children. Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative, safe and effective medications in the treatment of this disorder. Theophylline is a psychomotor stimulant most widely used as a broncodilator. Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders. We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylphenidate for the treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were randomized to theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2) for a 6-week double-blind and randomized clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist, at baseline and at 14, 28 and 42 days after start of the medication. No significant differences were observed between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores over the trial ( t = 0·49, d.f. = 24 P = 0·62 and t = 0·19, d.f. = 24 P = 0·54 respectively). Although the number of dropouts in the methylphenidate group was higher than the theophylline group, there was no significant difference between the two protocols in terms of the dropouts. In addition, headaches were observed more often in the methylphenidate group. The results suggest that theophylline may be a useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD. Nevertheless, our study is small and our results would need to be confirmed in a larger study. [ABSTRACT FROM AUTHOR]

What is known and objective Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl- d-aspartate receptor antagonist, in humans. Methods Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale ( HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. Results and discussion A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 ( P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group ( P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine ( P < 0·001, Cohen's d = 12·71) and placebo groups ( P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. What is new and conclusion A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. [ABSTRACT FROM AUTHOR]

What is known and objective: N-acetylcysteine (NAC) has been proposed as a potential therapy for obsessive-compulsive disorder (OCD) as it may regulate the exchange of glutamate and prevent its pre-oxidant effects. The aim of the present double-blind, placebo-controlled trial was to assess the efficacy and tolerability of NAC augmentation in moderate-to-severe (OCD) treatment. Methods: In this randomized, double-blind, two-centre, placebo-controlled, 10-week trial, patients with moderate-to-severe OCD were enrolled. Patients were randomized into two parallel groups to receive fluvoxamine (200 mg daily) plus placebo or fluvoxamine (200 mg daily) plus NAC (2000 mg daily). A total of 44 patients (22 in each group) were visited to evaluate response to therapy using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at baseline, and at weeks 4, 8 and 10. Side effects were recorded using predesigned checklists upon each visit. Results and discussion: Repeated-measures ANOVA showed a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5.14, d.f. = 1.64, P = 0.012) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5.44, d.f. = 1.54, P = 0.011) in the Y-BOCS obsession subscale between the two groups. What is new and conclusion: Our results showed that NAC might be effective as an augmentative agent in the treatment of moderate-to-severe OCD. Trial registration: Iranian Registry of Clinical Trials (www.irct. ir): IRCT201405271556N60 [ABSTRACT FROM AUTHOR]

What is known and objective Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate. Inflammatory processes are involved in the pathogenesis of both brucellosis and depression. Therefore, we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis. Methods Forty outpatients with depression due to brucellosis with a Hamilton Depression Rating Scale score ( HDRS) <19 participated in a randomized, double-blind, placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib (200 mg bid) or placebo as an adjunctive to antibiotic therapy. Patients were evaluated using HDRS at baseline and weeks 4 and 8. Result and discussion Repeated-measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [ F (1·43, 57·41) = 37·22, P < 0·001]. Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [10 patients (50%) vs. no patient (0%), respectively, P < 0·001]. No serious adverse event was observed. What is new and conclusion Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo. [ABSTRACT FROM AUTHOR]

Introduction: A growing body of evidence implicates inflammatory cascades in the pathophysiology of obsessive-compulsive disorder (OCD), making this pathway a target for development of novel treatments. Methods: 50 outpatients with moderate to severe OCD participated in the trial, and underwent 10 weeks of treatment with either celecoxib (200 mg twice daily) or placebo as an adjuvant to fluvoxamine. Participants were investigated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the efficacy of celecoxib in improving the OCD symptoms. Results: General linear model repeated measures demonstrated significant effect for time × treatment interaction on the Y-BOCS total scores [F (1.38, 66.34) = 6.91, p = 0.005]. Kaplan-Meier estimation with log-rank test demonstrated significantly more rapid response in the celecoxib group than the placebo group (p < 0.001). There was no significant difference in adverse event frequencies between the groups. Discussion: The results of the current study suggest that celecoxib could be a tolerable and effective adjunctive treatment for more rapid and more satisfying improvements in OCD symptoms. [ABSTRACT FROM AUTHOR]

Background: Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks.Objective: The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia.Study Design: This was an 8-week, randomized, double-blind, placebo-controlled study.Study Setting: Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.Patients: Forty patients (male and female gender) aged 18-50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study.Interventions: The patients were randomly assigned to oxytocin intranasal spray (Syntocinon(®); Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day).Outcomes: The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8.Results: All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p < 0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p < 0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen's d = 1.2, 20 % vs. 4 % reduction in score, p < 0.001), negative (Cohen's d = 1.4, 7 % vs. 2 % reduction in score, p < 0.001) and general psychopathology (Cohen's d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen's d = 1.9, 11 % vs. 2 % reduction in score, p < 0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups.Conclusion: Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients. [ABSTRACT FROM AUTHOR]

Objective The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). Design Double-blind, randomised and placebo-controlled trial. Setting Departments of Gynaecology/Obstetrics and Psychiatry, Tehran and Zanjan University of Medical Sciences. Population Women aged 20–45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. Method Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) (group A) or capsule placebo (twice a day) for a two menstrual cycles (cycles 3 and 4). Main outcome measures The primary outcome measure was the Daily Symptom Report, and secondary outcome measure was the Hamilton Depression Rating Scale. Results In this trial, saffron was found to be effective in relieving symptoms of PMS. A significant difference was observed in efficacy of saffron in cycles 3 and 4 in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. Conclusion The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS. However, a tolerable adverse effects profile of saffron may well confirm the application of saffron as an alternative treatment for PMS. These results deserved further investigations. [ABSTRACT FROM AUTHOR]

Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder.Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score≥18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6.Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0·001). There was no statistically significant difference between the mean ± SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (≥50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of≤7). None of the differences in reported adverse events was statistically significant.In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder. [ABSTRACT FROM AUTHOR]

Introduction: Opium tincture (OT) is widely used for opioid substitution treatment (OST) in Iran. Objectives: To determine if OT is a safe and effective medication for OST. Methods: Opium Trial was a multicenter, double-blind, noninferiority randomized controlled trial, with 204 participants with opioid dependence in Iran. Participants were then randomized to OT or methadone arms with an allocation ratio of 1:1 and were followed for 12 weeks. The primary outcome was retention in treatment, compared between the two groups using both intention-To-Treat (ITT) and Per-Protocol (PP) analyses. Results: A total of 70 participants (IT: 68.6%, PP: 69.3%) in methadone arm and 61 participants (ITT: 59.8%, PP: 60.4%) in OT arm remained in the treatment. The relative retention rate was 1.15 (0.97, 1.36) in both analyses in favour of methadone. A total of 46 out of 152 (30.3%) participants in OT arm and 83 out of 168 (49.4%) participants in methadone arm reported opioid use outside the treatment. The difference in these two proportions (OT - methadone) was 19%: (10%, 28%) in favour of OT. The proportion of patients with adverse eventswere not different between the two arms (P = 0.06). There was no serious AE in OT arm. Conclusions: Opium tincture is a clinically effective and safe medication, but this study could not conclude if it was as equally effective as methadone in retaining participants in treatment, but it showed that OT was superior to methadone in reducing opioid use outside the treatment. [ABSTRACT FROM AUTHOR]

Abstract: This cross-sectional study evaluated the prevalence of major depressive disorder and depressive symptoms in children and adolescents after renal transplantation. A total of 71 patients who had undergone renal transplantation were interviewed in person using the Farsi (Persian) version of the Kiddie Schedule for Affective Disorders and Schizophrenia and Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria. Major depressive disorder, depressive symptoms, and suicidal behaviors were assessed. The rate of major depressive disorder was 2.8%; two-thirds of the patients had irritability; and approximately 40% had recurrent thoughts of death and suicidal ideation. The rate of major depressive disorder was lower than in other chronic diseases such as thallasemia or hemophilia; however, the rate of suicidal behaviors was high. [Copyright &y& Elsevier]

Introduction: Cyclic changes in symptomatology, sleep disorders and changes in body temperature in bipolar disorder suggest a circadian rhythm disorder and its most important regulator, melatonin. Folate is both a melatonin enhancer and has been shown to be lower in manic patients. Objectives: To investigate the association between melatonin level (by its most important metabolite, urinary 6-sulfatoxymelatonin) and clinical score of bipolar patients after folate supplementation of their medication. Methods: Forty eight patients (who had at least one manic episode based on DSM-IV) were included in the study and out of these patients 8 patients dropped out during the study due to changes in diagnosis and 40 were randomized to group A (21 patients, folic acid+lithium+resperidone) and group B (19 patient, placebo +lithium+resperidone). Also 8 controls were selected for comparison of urinary 6 sulfatoxymelatonin levels. Morning Urinary 6 sulfatoxy melatonin and Young Mania Rating Scale were measured in the beginning and at the end of the first month. Results: There were significant differences between group A and B in the alteration of level of urinary 6-sulfatoxymelatonin measured during the study period(11.7±13.4 Vs -6±16.2 p< 0.001)both groups had significantly lower 6MT than controls and this persisted till the end of the first month in both groups. Significant difference was seen between alteration of YMRS in two groups(34.5±3.9 Vs 30.1±3.8 p< 0.001). Conclusion: Our findings showed that folic acid may be effective as an adjunct to main mania treatment, and it may exert its effect partially due to changes in melatonin profile. [ABSTRACT FROM AUTHOR]